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Gene Review

GRN  -  granulin

Homo sapiens

Synonyms: CLN11, GEP, GP88, Granulins, PCDGF, ...
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Disease relevance of GRN


Psychiatry related information on GRN

  • There was a strong correlation between Pepi and GGEMG during wakefulness in most subjects (9 of 15 had absolute R > 0.7 [p < 0.05], group mean R = -0.62, p < 0.05) [6].

High impact information on GRN


Chemical compound and disease context of GRN


Biological context of GRN


Anatomical context of GRN


Associations of GRN with chemical compounds

  • Previous studies showed that the granulin/epithelin precursor (GEP) binds the histidine-rich region of cyclin T1 and inhibits P-TEFb function [3].
  • It is thus suggested that the cysteine-rich domain of Tat plays a role in the interaction between the Tat and either Notch2 or the epithelin/granulin domains, both of which exhibit EGF-like-repeat-imposed spatial conformation [9].
  • Furthermore, binding experiments demonstrated that CSBG bound to glycosphingolipids (such as LacCer) with a terminal galactose residue; however, SCG and GRN (1,6-monoglucosyl-branched beta-glucans) did not bind to LacCer [16].
  • Gel forming 6 branched (1----3)-beta-D-glucans, SSG, branched at every other main chain glucosyl unit, grifolan (GRN) and schizophyllan, branched at one third of main chain glucosyl unit, enhanced clot formation of human plasma [17].
  • Effect of postmenopausal hormone therapy on lipoprotein(a) concentration. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions [18].

Regulatory relationships of GRN


Other interactions of GRN

  • Sequencing the region surrounding the human alphaIIb locus showed the Granulin gene approximately 18 kb downstream to alphaIIb, and the KIAA0553 gene approximately 5.7 kb upstream [21].
  • Our study provides the first evidence of high incidence of PCDGF expression in human breast cancer in which it correlates with clinicopathological variables such as tumor grade, proliferation index, and p53 expression [14].
  • Average Ki-67 index of PCDGF-negative/weakly positive invasive carcinomas (30.3) was significantly lower than that of strongly PCDGF-positive tumors (48.8, P=0.01) [14].
  • It is assumed that such interactions might modulate the physiological functions of Notch2 and epithelin/granulin, thereby affecting various pathologies associated with CAEV [9].
  • Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production, reduction in cell growth (P < 0.002), decrease in the S-phase fraction (P < 0.04), and loss of density-independent growth potential (P < 0.01) [4].

Analytical, diagnostic and therapeutic context of GRN

  • The GEP RNA level was examined by quantitative reverse transcription-PCR, and protein localization by immunohistochemistry [13].
  • Our earlier cDNA microarray study indicated that GEP was overexpressed in hepatocellular carcinoma (HCC) [13].
  • CONCLUSION: These data suggest that expression of PCDGF/GP88 confers resistance to dexamethasone and increase tumorigenesis of multiple myeloma cells in mouse xenografts [22].
  • Comparison of mRNA levels by semi-quantitative RT-PCR revealed a relative overexpression of three genes in cancer tissues, including growth factor granulin and Tbdn-1--an orthologue of the mouse acetyltransferase gene which is associated with blood vessel development [23].
  • T. ni larval bioassays showed that a factor, present in the TnGV granulin or AcMNPV polyhedrin, enhanced the infectivity of AcMNPV [24].


  1. Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor). Zhang, H., Serrero, G. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption. Liau, L.M., Lallone, R.L., Seitz, R.S., Buznikov, A., Gregg, J.P., Kornblum, H.I., Nelson, S.F., Bronstein, J.M. Cancer Res. (2000) [Pubmed]
  3. Granulin and granulin repeats interact with the Tat.P-TEFb complex and inhibit Tat transactivation. Hoque, M., Tian, B., Mathews, M.B., Pe'ery, T. J. Biol. Chem. (2005) [Pubmed]
  4. The granulin-epithelin precursor/PC-cell-derived growth factor is a growth factor for epithelial ovarian cancer. Jones, M.B., Michener, C.M., Blanchette, J.O., Kuznetsov, V.A., Raffeld, M., Serrero, G., Emmert-Buck, M.R., Petricoin, E.F., Krizman, D.B., Liotta, L.A., Kohn, E.C. Clin. Cancer Res. (2003) [Pubmed]
  5. PC cell-derived growth factor expression in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Pan, C.X., Kinch, M.S., Kiener, P.A., Langermann, S., Serrero, G., Sun, L., Corvera, J., Sweeney, C.J., Li, L., Zhang, S., Baldridge, L.A., Jones, T.D., Koch, M.O., Ulbright, T.M., Eble, J.N., Cheng, L. Clin. Cancer Res. (2004) [Pubmed]
  6. Genioglossal but not palatal muscle activity relates closely to pharyngeal pressure. Malhotra, A., Pillar, G., Fogel, R.B., Beauregard, J., Edwards, J.K., Slamowitz, D.I., Shea, S.A., White, D.P. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  7. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Zhu, J., Nathan, C., Jin, W., Sim, D., Ashcroft, G.S., Wahl, S.M., Lacomis, L., Erdjument-Bromage, H., Tempst, P., Wright, C.D., Ding, A. Cell (2002) [Pubmed]
  8. Mediation of estrogen mitogenic effect in human breast cancer MCF-7 cells by PC-cell-derived growth factor (PCDGF/granulin precursor). Lu, R., Serrero, G. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  9. The Tat protein of the caprine arthritis encephalitis virus interacts with the Notch2 EGF-like repeats and the epithelin/granulin precursor. Shoham, N., Cohen, L., Gazit, A., Yaniv, A. Intervirology (2003) [Pubmed]
  10. PC cell-derived growth factor mediates tamoxifen resistance and promotes tumor growth of human breast cancer cells. Tangkeangsirisin, W., Hayashi, J., Serrero, G. Cancer Res. (2004) [Pubmed]
  11. Lysophosphatidic acid and endothelin-induced proliferation of ovarian cancer cell lines is mitigated by neutralization of granulin-epithelin precursor (GEP), a prosurvival factor for ovarian cancer. Kamrava, M., Simpkins, F., Alejandro, E., Michener, C., Meltzer, E., Kohn, E.C. Oncogene (2005) [Pubmed]
  12. Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. Bhandari, V., Palfree, R.G., Bateman, A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  13. Granulin-epithelin precursor overexpression promotes growth and invasion of hepatocellular carcinoma. Cheung, S.T., Wong, S.Y., Leung, K.L., Chen, X., So, S., Ng, I.O., Fan, S.T. Clin. Cancer Res. (2004) [Pubmed]
  14. Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium. Serrero, G., Ioffe, O.B. Hum. Pathol. (2003) [Pubmed]
  15. Structure and chromosomal location of the human granulin gene. Bhandari, V., Bateman, A. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  16. Induction of human neutrophil chemotaxis by Candida albicans-derived beta-1,6-long glycoside side-chain-branched beta-glucan. Sato, T., Iwabuchi, K., Nagaoka, I., Adachi, Y., Ohno, N., Tamura, H., Seyama, K., Fukuchi, Y., Nakayama, H., Yoshizaki, F., Takamori, K., Ogawa, H. J. Leukoc. Biol. (2006) [Pubmed]
  17. Enhancement of clot formation of human plasma by beta-glucans. Ohno, N., Suzuki, T., Saito, K., Yadomae, T. J. Pharmacobio-dyn. (1990) [Pubmed]
  18. Effect of postmenopausal hormone therapy on lipoprotein(a) concentration. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Espeland, M.A., Marcovina, S.M., Miller, V., Wood, P.D., Wasilauskas, C., Sherwin, R., Schrott, H., Bush, T.L. Circulation (1998) [Pubmed]
  19. PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells. Tangkeangsirisin, W., Serrero, G. Carcinogenesis (2004) [Pubmed]
  20. Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468. Lu, R., Serrero, G. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  21. The human platelet alphaIIb gene is not closely linked to its integrin partner beta3. Thornton, M.A., Poncz, M., Korostishevsky, M., Yakobson, E., Usher, S., Seligsohn, U., Peretz, H. Blood (1999) [Pubmed]
  22. PC cell-derived growth factor confers resistance to dexamethasone and promotes tumorigenesis in human multiple myeloma. Wang, W., Hayashi, J., Serrero, G. Clin. Cancer Res. (2006) [Pubmed]
  23. Serological identification and expression analysis of gastric cancer-associated genes. Linē, A., Stengrēvics, A., Slucka, Z., Li, G., Jankevics, E., Rees, R.C. Br. J. Cancer (2002) [Pubmed]
  24. Alteration of a lepidopteran peritrophic membrane by baculoviruses and enhancement of viral infectivity. Derksen, A.C., Granados, R.R. Virology (1988) [Pubmed]
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